This proposal focuses on the design and development of a scalable PET detector with depth-of-interaction (DOI) positioning capability. The basic module design will be suitable for high resolution, small animal PET imaging and clinical, time-of-flight (TOF), whole body PET imaging. The PET detector will be compatible with operation in a MR scanner. The design will utilize a low cost, thick, monolithic crystal scintillator readout by a two-dimensional array of silicon photomultiplier (SiPM) devices. A novel feature of our design is that the sensors will only be placed on the entrance surface of the scintillation detector. Preliminary results indicate that both the intrinsic X, Y spatial resolution and the effective DOI positioning accuracy are improved using the sensor on entrance plane (SEP) design versus traditional placement of the sensors on the far surface of the crystal. A key aspect of the design is the integration of the readout electronics with the detection system. To support TOF PET, a special hybrid application specific integrated circuit (ASIC) will be developed and the fist level of signal amplification will be kept as close as possible to the SiPM device using a custom pre-amplifier tile that can be placed on the entrance surface of the detector. Further, all electronics will be selected so that the detector can operate in a magnetic field environment to support PET/MRI. A 'universal' detector module that can be scaled between human whole-body, human brain, and preclinical PET imaging systems will be developed. Further, a prototype small animal PET system will be built and evaluated within this proposal. The prototype system will provide full proof of principle of the design concept. This will be especially valuable in assessing the benefits of having DOI information. In addition a set of whole- body detector modules will be built and evaluated in a gantry simulator for both their TOF, coincidence timing characteristics and potential image resolution benefits that will be provided by having both TOF and DOI positioning information. This joint research proposal brings together the University of Washington PET physics group with a long and fertile contribution to the field of nuclear and pre-clinical instrumentation and Philips, Nuclear Medicine Business Unit, with a very active research program in PET imaging and demonstrated leadership in Time-of- Flight technology and reconstruction. PUBLIC HEALTH RELEVANCE: According to the American Cancer Society one out of every two males and one out of every three females in the United States will develop cancer during their lifetime. Of individuals developing cancer about one half will die from the disease. Therefore the goal of this work is to develop new imaging technology that will aid in the battle against cancer. To do this, the detector technology that we are developing will advance the state of the art for both whole body PET/CT imaging and small animal, preclinical PET imaging systems. It will provide timing performance to support time-of-flight imaging for human, whole-body imaging protocols. The detector will also be MR compatible to support combined PET/MR imaging for both small animals and for humans. Finally, the detector will provide depth of interaction (DOI) information. DOI information will support both PET/MR imaging and provide a better combination of intrinsic spatial resolution and detection efficiency for small animal imaging systems.